ArticleEMBO molecular medicine2012
WLS inhibits melanoma cell proliferation through the β-catenin signalling pathway and induces spontaneous metastasis.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- EVI/WLS function is regulated by ubiquitylation and is linked to ER-associated degradation by ERLIN2.Journal of cell science · 2021Article
- SILAC-Based Quantitative Proteomic Analysis of Oxaliplatin-Resistant Pancreatic Cancer Cells.Cancers · 2021Article
- Article
- ERAD-dependent control of the Wnt secretory factor Evi.The EMBO journal · 2018Article
- Pharmacological interventions in the Wnt pathway: inhibition of Wnt secretion versus disrupting the protein-protein interfaces of nuclear factors.British journal of pharmacology · 2017Review
- Structure-based mutational analysis of ICAT residues mediating negative regulation of β-catenin co-transcriptional activity.PloS one · 2017Article
- G Protein-Coupled Receptor Signaling in Stem Cells and Cancer.International journal of molecular sciences · 2016Review
- Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs.Cell research · 2016Article
- Wls promotes the proliferation of breast cancer cells via Wnt signaling.Medical oncology (Northwood, London, England) · 2015Article
- Updating the Wnt pathways.Bioscience reports · 2014Article
- WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors.The Journal of clinical investigation · 2014Article
- Melanoma metastasis: new concepts and evolving paradigms.Oncogene · 2014Review
- Single-cell imaging of Wnt palmitoylation by the acyltransferase porcupine.Nature chemical biology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Elevated levels of nuclear β-catenin are associated with higher rates of survival in patients with melanoma, raising questions as to how ß-catenin is regulated in this context. In the present study, we investigated the formal possibility that the secretion of WNT ligands that stabilize ß-catenin may be regulated in melanoma and thus contributes to differences in ß-catenin levels. We find that WLS, a conserved transmembrane protein necessary for WNT secretion, is decreased in both melanoma cell lines and in patient tumours relative to skin and to benign nevi. Unexpectedly, reducing endogenous WLS with shRNAs in human melanoma cell lines promotes spontaneous lung metastasis in xenografts in mice and promotes cell proliferation in vitro. Conversely, overexpression of WLS inhibits cell proliferation in vitro. Activating β-catenin downstream of WNT secretion blocks the increased cell migration and proliferation observed in the presence of WLS shRNAs, while inhibiting WNT signalling rescues the growth defects induced by excess WLS. These data suggest that WLS functions as a negative regulator of melanoma proliferation and spontaneous metastasis by activating WNT/β-catenin signalling.
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Registered trials
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